Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans

Background Preclinical evidence implicates the serotonin receptor 5-hydroxytryptamine 1B (5-HT 1B ) in the effects of cocaine. This study explores 5-HT 1B in humans by examining receptor availability in vivo in subjects whose primary addiction is cocaine dependence (CD) using positron emission tomography. Methods Study participants included 14 medically healthy subjects with CD (mean age=41 ± 6 years) who were compared with 14 age-matched healthy control subjects (mean age=41 ± 8 years) with no past or current history of cocaine or other illicit substance abuse. Participants underwent magnetic resonance imaging followed by positron emission tomography with the highly selective 5-HT 1B tracer, [ 11 C]P943, for purposes of quantifying regional binding potential. Voxel-based morphometry and gray matter masking also were employed to control for potential partial volume effects. Results The [ 11 C]P943 positron emission tomography imaging data in nine candidate regions (amygdala, anterior cingulate cortex, caudate, frontal cortex, hypothalamus, pallidum, putamen, thalamus, and ventral striatum) showed significant or nearly significant reductions of regional binding potential in subjects with CD in three regions: anterior cingulate (−16%, p p = .03), and frontal cortex (−7%, p = .08). Voxel-based morphometry showed significant gray matter reductions in the frontal cortex of subjects with CD. After gray matter masking, statistically significant reductions in the [ 11 C]P943 regional binding potential were either retained (anterior cingulate, −14%, p = .01; hypothalamus, −20%, p p Conclusions The reductions found in this study suggest that 5-HT 1B receptors may contribute to the etiology or expression of CD and potentially represent a target for medication development.